CHAPTER 15 THE CHROMOSOMAL BASIS OF INHERITANCE Section B: Sex Chromosomes 1. The chromosomal basis of sex varies with the organism 2. Sex-linked genes have unique patterns of inheritance
1. The chromosomal basis of sex varies with the organism Although the anatomical and physiological differences between women and men are numerous, the chromosomal basis of sex is rather simple. In human and other mammals, there are two varieties of sex chromosomes, X and Y. An individual who inherits two X chromosomes usually develops as a female. An individual who inherits an X and a Y chromosome usually develops as a male.
This X-Y system of mammals is not the only chromosomal mechanism of determining sex. Other options include the X-0 system, the Z-W system, and the haplodiploid system. Fig. 15.8
In the X-Y system, Y and X chromosomes behave as homologous chromosomes during meiosis. In reality, they are only partially homologous and rarely undergo crossing over. In both testes (XY) and ovaries (XX), the two sex chromosomes segregate during meiosis and each gamete receives one. Each egg receives an X chromosome. Half the sperm receive an X chromosome and half receive a Y chromosome. Because of this, each conception has about a fiftyfifty chance of producing a particular sex.
In humans, the anatomical signs of sex first appear when the embryo is about two months old. In individuals with the SRY gene (sex determining region of the Y chromosome), the generic embryonic gonads are modified into testes. Activity of the SRY gene triggers a cascade of biochemical, physiological, and anatomical features because it regulates many other genes. In addition, other genes on the Y chromosome are necessary for the production of functional sperm. In individuals lacking the SRY gene, the generic embryonic gonads develop into ovaries.
2. Sex-linked genes have unique patterns of inheritance In addition to their role in determining sex, the sex chromosomes, especially the X chromosome, have genes for many characters unrelated to sex. These sex-linked genes follow the same pattern of inheritance as the white-eye locus in Drosophila. Fig. 15.9
If a sex-linked trait is due to a recessive allele, a female have this phenotype only if homozygous. Heterozygous females will be carriers. Because males have only one X chromosome (hemizygous), any male receiving the recessive allele from his mother will express the trait. The chance of a female inheriting a double dose of the mutant allele is much less than the chance of a male inheriting a single dose. Therefore, males are far more likely to inherit sexlinked recessive disorders than are females.
Several serious human disorders are sex-linked. Duchenne muscular dystrophy affects one in 3,500 males born in the United States. Affected individuals rarely live past their early 20s. This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin. The disease is characterized by a progressive weakening of the muscles and loss of coordination.
Hemophilia is a sex-linked recessive trait defined by the absence of one or more clotting factors. These proteins normally slow and then stop bleeding. Individuals with hemophilia have prolonged bleeding because a firm clot forms slowly. Bleeding in muscles and joints can be painful and lead to serious damage. Individuals can be treated with intravenous injections of the missing protein.
Although female mammals inherit two X chromosomes, only one X chromosome is active. Therefore, males and females have the same effective dose (one copy ) of genes on the X chromosome. During female development, one X chromosome per cell condenses into a compact object, a Barr body. This inactivates most of its genes. The condensed Barr body chromosome is reactivated in ovarian cells that produce ova.
Mary Lyon, a British geneticist, has demonstrated that the selection of which X chromosome to form the Barr body occurs randomly and independently in embryonic cells at the time of X inactivation. As a consequence, females consist of a mosaic of cells, some with an active paternal X, others with an active maternal X. After Barr body formation, all descendent cells have the same inactive X. If a female is heterozygous for a sex-linked trait, approximately half her cells will express one allele and the other half will express the other allele.
In humans, this mosaic pattern is evident in women who are heterozygous for a X-linked mutation that prevents the development of sweat glands. A heterozygous woman will have patches of normal skin and skin patches lacking sweat glands.
Similarly, the orange and black pattern on tortoiseshell cats is due to patches of cells expressing an orange allele while others have a nonorange allele. Fig. 15.10
X inactivation involves the attachment of methyl (CH 3 ) groups to cytosine nucleotides on the X chromosome that will become the Barr body. One of the two X chromosomes has an active XIST gene (X-inactive specific transcript). This gene produces multiple copies of an RNA molecule that almost cover the X chromosome where they are made. This initiates X inactivation, but the mechanism that connects XIST RNA and DNA methylation is unknown. What determines which of the two X chromosomes will have an active XIST gene is also unknown.